For the first time in history a stem cell drug has been approved for market authorization.

Prochymal® (remestemcel-L) is also the first drug to be approved for the treatment of acute graft-vs-host disease (GvHD) in children, a devastating complication of bone marrow transplantation that kills almost 80% of all affected children, many of which just weeks after they have been diagnosed.

GvHD is the leading cause of transplant-related mortality, caused by an immunologic attack. Severe GvHD can cause blistering of the skin, intestinal hemorrhage and liver failure and is extremely painful with a death rate of up to 80%. At present, the first-line standard therapies for GvHD are steroids. Given that the success rate of steroids is only 30 to 50%, the only other therapy if steroids fail is limited to immunosuppressive agents that are used off-label with little benefit and significant toxicities. Until the approval of Prochymal, there has not been any other therapy for GvHD.

Osiris Therapeutics Inc. was awarded authorization for Prochymal under Health Canada's Notice of Compliance with conditions (NOC/c). A NOC/c is an authorization to market a drug with the condition that the manufacturer undertakes additional studies to verify the clinical benefit. This pathway provides access to treatments for unmet medical conditions and has demonstrated its benefits outweigh its risks in clinical trials.

Andrew Daly, M.D., Clinical Associate Professor from the Department of Medicine and Oncology at the University of Calgary, Canada and leading researcher of Prochymal's phase 3 clinical program declared:

"I am very proud of the leadership role Canada has taken in advancing stem cell therapy and particularly gratified that this historic decision benefits children who would otherwise have little hope. As a result of Health Canada's comprehensive review, physicians now have an off-the-shelf stem cell therapy in their arsenal to fight GvHD. Much like the introduction of antibiotics in the late 1920's, with stem cells we have now officially taken the first step into this new paradigm of medicine."

C. Randal Mills, Ph.D., President and Chief Executive Officer of Osiris announced:

"Today is not only a great day for Osiris, but for everyone involved in the responsible development of stem cell therapies. Most importantly, today is a great day for children and their families who bravely face this horrific disease. While today marks the first approval of a stem cell drug, now that the door has been opened, it will surely not be the last."

Prochymal is an intravenous formulation of mesenchymal stem cells (MSCs), which are derived from the bone marrow of healthy adult donors aged between 18 and 30 years. The MSCs are selected from the bone marrow and grown in culture, producing up to 10,000 doses of Prochymal from a single donor. The drug is a true off-the-shelf stem cell product, which is stored frozen until it is needed. Prochymal is infused through a simple intravenous line without the need to type or immunosuppress the recipient. The drug is currently undergoing Phase 3 trials for refractory Crohn's disease, as well as undergoing clinical trials for the treatment of heart attacks and type-1 diabetes.

Health Canada granted the Prochymal's authorization for the management of acute GvHD in children who are unresponsive to steroids, based on the drug's results of clinical trials. Prochymal was recommended by an independent expert advisory panel, which was commissioned to assess the drugs safety and efficacy.

The trials demonstrated that in 61 to 64% of children with acute GvHD who were unresponsive to steroids, Prochymal produced a clinically significant response at 28 days after the start of the therapy. Compared with a historical control population of pediatric patients with refractory GvHD (p=0.028), Prochymal also demonstrated a statistically important improvement in survival, with the largest benefit of survival being noted in those with the most severe forms of GvHD. One of the conditions for approval is that Prochymal's clinical benefit will undergo further evaluation in a case matched confirmatory trial. All patients receiving Prochymal will be encouraged to participate in order to monitor the long-term effects of the therapy.

Joanne Kurtzberg, MD, Head of the Pediatric Bone Marrow Transplant Program at Duke University and Lead Investigator for Prochymal explains:

"Refractory GvHD is not just deadly to the patients it afflicts, but is devastating for the family, friends, and caregivers who watch helplessly as the disease progresses. I have personally seen Prochymal reverse the debilitating effects of severe GvHD in many of my patients and now, after nearly two decades of research, the data demonstrating consistently high response rates, a strong safety profile and improved survival clearly support the use of Prochymal in the management of refractory GvHD."

Prochymal will be commercially available in Canada later this year and is currently available for adults and children under an Expanded Access Program (EAP) in various countries, including the U.S.

Peter Friedli, Chairman and Co-founder of Osiris declared:

"Today Osiris turns the promise of stem cell research into reality, delivering on decades of medical and scientific research. It took 20 years of hard work and perseverance and I want to personally thank everyone involved for their dedication to this important mission."

Osiris has an extensive intellectual property protection in terms of Prochymal, which includes 48 issued patents. Health Canada has also granted the company with an eight-year long regulatory exclusivity within the territory for Prochymal, with an additional 6-months extension on the basis that the drug is meant for the pediatric population.

Written By Petra Rattue